Interview with Associate Editor Aryeh Warmflash

Aryeh Warmflash

What inspired you to become a scientist?

As a child, I was always really interested in math. I loved figuring things out – working on problems that made sense and fit together logically. As I grew older, this passion expanded into physics, where I became fascinated by the idea of applying mathematical principles to understand the natural world. My curiosity shifted toward life sciences and how living systems work. I was captivated by the idea that the natural world can be described through equations, making it both understandable and predictable. Living organisms, however, are incredibly dynamic and complex – far more so than many of the systems traditionally studied in physics. This complexity is what ultimately drew me to biology. My research is driven by biological questions, but my physics background provides me with a set of quantitative tools and methods to tackle these questions effectively.

As a physicist, what ultimately drew you toward studying signalling dynamics and embryonic development?

I joined the lab of Aaron Dinner (University of Chicago, USA), which worked on modelling biological systems, and focused on nonequilibrium statistical mechanics, which is the branch of statistical mechanics that deals with systems out of thermodynamic equilibrium. During this time, I began collaborating with biologists studying gene regulatory networks and the development of the immune system. These collaborations sparked my interest in living systems, which are some of the most compelling examples of nonequilibrium systems. I started applying the tools and models I was developing to biology, aiming to understand how these systems operate. While I found these collaborative projects stimulating, I realised that I needed to engage with the experimental side of research. For my postdoc in the laboratories of Ali H. Brivanlou and Eric Siggia at The Rockefeller University, I moved beyond immune system development to explore spatial patterning and embryonic development. Initially, I studied early development in Xenopus embryos, but I eventually shifted my focus to cell cultures. Cell cultures provided a controlled environment where I could ask precise questions and make observations that would have been challenging to study directly in vivo. Using this system, I investigated how signalling pathways generate patterns and how self-organisation emerges. This approach felt like a perfect balance between theory and experiment, allowing me to address fundamental questions in developmental biology. For the past 15 years, this has been the primary focus of my research.

What is the main theme of your lab's research, and what questions are you currently investigating?

Our lab focuses on the early stages of human development, particularly gastrulation and neurulation, when the body axes and germ layers are established. Specifically, we investigate how signalling pathways such as BMP, Wnt, Nodal and FGF – key players in early development – coordinate to transform the relatively simple blastocyst into the complex organisation of the body plan. One major challenge in our work is the variability in stem cell cultures compared to the reproducibility of embryonic development. Early on, we identified geometry as a key factor – in traditional stem cell cultures, cells form irregular colonies, introducing significant variability. To address this, we use bioengineering techniques to carefully control colony shape and size (e.g. creating circular colonies of precise diameters). This approach improves reproducibility and allows us to generate models that mimic embryo-like patterns.

In our system, introducing a single growth factor, such as BMP, can trigger downstream signalling cascades (e.g. Wnt and Nodal) that self-organise into patterns resembling those observed in embryos. Remarkably, this occurs even in simplified, engineered environments, underscoring the inherent self-organising capabilities of these systems. One surprising discovery is that signalling in these colonies does not conform to the traditional ‘gradient model’ often depicted in textbooks. Instead of static gradients, we observe dynamic signalling fronts propagating through the colony. These fronts drive differentiation, with the cells' responses determined by the timing and relative dynamics of multiple signals. This highlights that much of the critical information for patterning lies in the temporal dynamics of signalling, rather than solely in the final steady-state levels.

What elements, inside or outside the lab, have been key to your success in science so far?

Science is a long-term commitment, whether it's a project, a graduate programme or a career. Having an intrinsic excitement about the work makes it much easier to stay motivated through the challenges. As a PI, building and maintaining a positive lab culture has been the most important factor. I've been fortunate to recruit talented and collaborative individuals who helped establish a culture where people are both enthusiastic about the scientific questions and happy to come to work. This culture has been self-sustaining, and I attribute much of the lab's success to it. While there's no precise formula for achieving this, I believe it's about choosing the right people, aligning on shared goals, and then giving them the space to explore and figure things out independently. One of the most rewarding aspects of being a PI is seeing how much the people in the lab grow. Now, they know far more than I do about the experimental techniques and specific details of their projects. My role has shifted to mentoring, guiding directions and fostering a collaborative atmosphere. It's both humbling and gratifying to witness the lab thriving on its collective expertise.

On a personal level, my background as a theorist has shaped my approach. While I don't do bench experiments, I've always loved imaging, analysing data and developing models. Those are areas where I still actively contribute. Many of the students who join my lab have strong experimental skills but limited experience in coding or modelling. Teaching and collaborating with them in these areas is something I enjoy and find meaningful. Outside the lab, the broader scientific community and the collaborations we've formed have been invaluable. Interacting with colleagues who bring different perspectives and expertise has enriched our research and broadened my understanding. Success in science isn't just about individual effort; it's about being part of an ecosystem that fosters curiosity, creativity and mutual support.

What recent discoveries in your field do you find the most exciting?

There's been a huge wave of technical progress in recent years, which I find incredibly exciting, although I think we haven't fully capitalised on it yet. One of the most obvious advances is the rapid development of embryo models. In the past few years, we've seen models that go to later stages of development and are becoming increasingly sophisticated and realistic. However, most of these studies are still in the proof-of-principle stage. We haven't yet exploited their full potential for understanding development. A key challenge, though, is reproducibility – achieving consistency from one embryo-like object to the next. Often, we see beautiful images in papers, but when we dive into the data, we find that only a small fraction of the structures in the culture dish has the expected phenotype, while the others display a wide range of variations. So, while these models are exciting, there's still significant work to be done to make them more consistent and reliable. On the technical side, we've seen immense progress, especially with the advent of CRISPR technology. When I first started my postdoc, CRISPR didn't even exist. Back then, we were using methods like overexpressing fluorescent fusion proteins to study signal transduction, which can introduce significant artifacts. Now, we can knock in fluorescent proteins directly onto ligands or signal transducers, which is a game-changer in terms of precision and efficiency.

Microscopy has also advanced dramatically, allowing us to capture much higher resolution and more dynamic images of development. With these improvements in both CRISPR technology and imaging, we now can tackle long-standing questions in developmental biology that were previously out of reach. It feels like we're on the cusp of making real strides in answering fundamental questions in the next few years, or at least over the course of my career. There's still a lot to be done, but the potential is exciting.

Throughout your career, what have been your approaches to establishing and maintaining good collaborations?

Collaboration in science has often been somewhat stochastic for me – more of a ‘bumping into people’ kind of process. You meet someone at a conference or a meeting, and you realise they have a unique expertise or resource that could really complement your work. In science, it's impossible to be an expert in everything, and no lab has the resources to do it all. So, collaborations are often born out of mutual recognition of the complementary strengths each group brings to the table. For example, we've had collaborations where other groups see our micro-patterning system and think, ‘That's exactly what we need to study our knockout cell line’. In these cases, they may send us their knockout, and we run it in our system, helping to reveal new phenotypes or gain insights that weren't possible before. We've also had collaborations where people approach us because they think our system can help them answer important biological questions they're struggling with. We've been fortunate that the tools and methods we've developed have been helpful to others, and we try to share those resources. In terms of maintaining good collaborations, I think it's crucial to be clear about what each party can bring to the table and where you might need each other's help. I make sure the goals are clear and the roles are well defined, so that both sides get value from the partnership. That's been key to fostering long-term collaborations.

What made you interested in taking on the role of Editor with JCS and what impact would you like to make in this role?

I've admired the work that The Company of Biologists does for a long time, and I see it as a valuable service to the scientific community. Their journals, conferences and overall support structure have made significant contributions to advancing research, so when the opportunity came up to be involved as an Editor with Journal of Cell Science, I was eager to contribute. JCS is looking to expand into areas like stem cells and quantitative biology, and I see that as an exciting challenge. The chance to influence how the journal approaches these topics and to help shape its direction in these rapidly advancing fields is something I find compelling. I think that bridging different scales in science, especially between the molecular and cellular biology of stem cells and the larger developmental processes in tissues and organisms, can lead to some of the most exciting discoveries. By helping to facilitate the integration of these perspectives, I hope to foster a community of researchers who are tackling these big questions from a variety of angles. In this role, I would like to encourage papers that connect cellular mechanisms to broader biological phenomena. I hope to build a sense of community around this type of integrative research, where cell biology intersects with systems biology. Additionally, I see this as an opportunity to learn from others in the field and bring that knowledge back to my own work. Overall, the impact I want to make is to help guide the journal's influence in fostering these cross-cutting, interdisciplinary ideas and growing the community of researchers exploring them.

How much do you read and how do you choose what you read?

The volume of scientific literature can be overwhelming, so I've become increasingly selective over time. A significant portion of my reading is driven by peer reviewing, which means I am constantly evaluating papers within my area of expertise. When reviewing, I ask myself if I can contribute something meaningful to the paper's evaluation – whether it aligns with my expertise or interests and whether my perspective can provide value. I also keep up with the literature through journal table of contents, particularly for journals that I would consider publishing in, and I set up Google Scholar alerts to track relevant developments. However, with the sheer volume of papers out there, I have two levels of reading. For many papers, I just skim them to understand what's out there, perhaps spending about 15 min to get a sense of the findings. These are typically papers on technical progress or advancements that are exciting but don't always warrant a deep dive. The smaller subset of papers I read more deeply tends to focus on fundamental scientific questions or novel approaches that are truly thought provoking. Overall, while the volume of literature grows, I think it's important to focus on the papers that are not only relevant but also scientifically compelling. It can sometimes feel like no one reads your own work given the vast amount of published research, but that's where a well-crafted abstract, title and figures really make a difference in catching attention.

What sort of papers would you like to see more of at JCS?

I'm particularly excited about papers that bridge different biological scales. For example, research that connects cell biology – especially stem cell biology – to larger developmental processes is something I would love to see more of at JCS. Papers that explore how the intricate mechanisms happening inside individual cells contribute to broader phenomena, like tissue patterning or the development of complex systems, are incredibly exciting. These types of studies can provide deeper insights into how cellular behaviours drive organismal development and can push the boundaries of both developmental biology and cell biology.

How would you like to see scientific publishing change in the future?

I think a big shift needs to happen away from the overwhelming emphasis on publishing in high-impact journals as a measure of a paper's importance. The current system creates an environment where career advancement and the perception of a study's significance are often linked to where it's published, rather than the quality or impact of the science itself. This focus distorts priorities and results in significant financial profits for journals that they don't always reinvest back into the scientific community. The rise of preprints has been a hugely positive development, particularly for biology, as it allows research to be disseminated and critiqued more quickly, without the delay of the traditional publishing process. In some fields, publishing has become almost anticlimactic because preprints are often available long before final journal publications. This shift has encouraged a more independent approach to evaluating science, moving away from relying on journal prestige.

Ideally, I would like to see a future where open access publishing becomes the norm, and journals that genuinely support the scientific community and reduce unnecessary barriers or costs are prioritised. However, the entrenched system around impact factors and journal prestige still heavily influences decisions, and that remains a challenge. So, while I don't know exactly what the answer is, I hope that with time, these attitudes will change and more sustainable models for science publishing will emerge.

What advice, on elements inside or outside the lab, would you give to young scientists developing their careers?

The most important advice I would give is to focus on working on things you're genuinely passionate about. If you care about what you're doing, it won't feel like a slog, and you'll be more motivated and productive. That said, maintaining a balance in your life is crucial – something I learned the hard way. When I was a trainee, I often worked long hours because I was genuinely interested in the work, but I also had a family to take care of. Now with more experience, I realise that balance is essential. Additionally, you need to recognise that your output isn't always proportional to the number of hours you put in. Working long hours doesn't mean you'll double your output, and overworking can lead to burnout. It's important to be intentional about how you spend your time. If you're intentional about your priorities and what you want to achieve, you'll feel more fulfilled. Otherwise, you'll end up at the end of the week thinking, ‘What did I actually accomplish?’ and feeling unsatisfied because it didn't align with your true priorities.

Finally, could you tell us an interesting fact about yourself that people wouldn't know by looking at your CV?

An interesting fact about me is that I'm a big crossword puzzle solver. I've been doing the New York Times crossword almost every day for years, and it's been a great hobby to disconnect from work. I find solving crossword puzzles relaxing, and it gives me a sense of accomplishment because everything fits together perfectly in the end, something that's harder to achieve in science, where things are often more complex and unresolved.

Aryeh Warmflash was interviewed by Sara Morais da Silva, Reviews Editor at Journal of Cell Science. This piece has been edited and condensed with approval from the interviewee.